Overview

Abstract (English)

BACKGROUND: Defining laboratory biomarker reference values in a healthy population and understanding the fluctuations in biomarker concentrations throughout life and between sexes are critical to clinical interpretation of laboratory test results in different disease states. The Canadian Health Measures Survey (CHMS) has collected blood samples and health information from the Canadian household population. In collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), the data have been analyzed to determine reference value distributions and reference intervals for several endocrine and special chemistry biomarkers in pediatric, adult, and geriatric age groups. METHODS: CHMS collected data and blood samples from thousands of community participants aged 3 to 79 years. We used serum samples to measure 13 immunoassay-based special chemistry and endocrine markers. We assessed reference value distributions and, after excluding outliers, calculated age- and sex-specific reference intervals, along with corresponding 90% CIs, according to CLSI C28-A3 guidelines. RESULTS: We observed fluctuations in biomarker reference values across the pediatric, adult, and geriatric age range, with stratification required on the basis of age for all analytes. Additional sex partitions were required for apolipoprotein AI, homocysteine, ferritin, and high sensitivity C-reactive protein. CONCLUSIONS: The unique collaboration between CALIPER and CHMS has enabled, for the first time, a detailed examination of the changes in various immunochemical markers that occur in healthy individuals of different ages. The robust age- and sex-specific reference intervals established in this study provide insight into the complex biological changes that take place throughout development and aging and will contribute to improved clinical test interpretation. Reference intervals partitioned according to the influence of key covariates, such as age and sex, provide insight into dynamic changes that occur in biochemical markers over the course of a lifetime and are essential when using these biomarkers in disease diagnosis, prognosis, or monitoring. Establishing accurate and robust reference intervals can be challenging due to the necessity of attaining a large and representative sample size of healthy individuals. Consequently, normative values are often established from patient data or are based on defunct methods. Although recent initiatives such as the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER),5 the Nordic Reference Interval Project, and others, have made great strides in establishing up-to-date reference intervals for disease biomarkers, major challenges still persist, including participant recruitment and cost (1-7). In 2007, The Canadian Health Measures Survey (CHMS) was launched to close data gaps within Canada’s health information system (8). The CHMS has sampled an extensive number of children and adults to produce a dataset that is representative of >96% of the Canadian population (8). The CALIPER project has now collaborated with Statistics Canada to extend and update its database to include age- and sex-stratified reference intervals for the pediatric through geriatric populations. This collaboration has resulted in a series of studies examining the changes in many chemistry, immunoassay, and hematology biomarkers, which provides valuable information beyond robust reference interval establishment. This extensive dataset, in combination with the consistency in participant selection and preanalytical, analytical, and postanalytical processes, allows determination of reference value distributions for various biochemical and hematologic markers and direct comparisons across various age ranges. In this report, we present reference values for 13 immunoassay-based biomarkers.

Abstract (French)

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